Novel lynx spider toxin shares common molecular architecture with defense peptides from frog skin

A unique 30‐residue cationic peptide oxyopinin 4a (Oxt 4a) was identified in the venom of the lynx spider Oxyopes takobius (Oxyopidae). Oxt 4a contains a single N‐terminally located disulfide bond, Cys4–Cys10, and is structurally different from any spider toxin studied so far. According to NMR findings, the peptide is disordered in water, but assumes a peculiar torpedo‐like structure in detergent micelles. It features a C‐terminal amphipathic α‐helical segment (body; residues 12–25) and an N‐terminal disulfide‐stabilized loop (head; residues 1–11), and has an unusually high density of positive charge in the head region. Synthetic Oxt 4a was produced and shown to possess strong and broad‐spectrum cytolytic and antimicrobial activity. cDNA cloning showed that the peptide is synthesized in the form of a conventional prepropeptide with an acidic prosequence. Unlike other arachnid toxins, Oxt 4a exhibits striking similarity with defense peptides from the skin of ranid frogs that contain the so‐called Rana‐box motif (a C‐terminal disulfide‐enclosed loop). Parallelism or convergence is apparent on several levels: the structure, function and biosynthesis of a lynx spider toxin are mirrored by those of Rana‐box peptides from frogs. Database The protein sequence of oxyopinin 4a (Oxt 4a) has been submitted to the UniProt Knowledgebase (UniProtKB) under the accession number P86350. The coordinates and chemical shifts of Oxt 4a in complex with dodecylphosphocholine micelles have been deposited in the Protein Data Bank and Biological Magnetic Resonance Bank under the accession codes 2L3I and 17194, respectively. The nucleotide sequence encoding Oxt 4a has been submitted to the EMBL Nucleotide Sequence Database under the accession number FN997582. A unique 30‐residue cationic peptide oxyopinin 4a (Oxt 4a) from the venom of Oxyopes takobius spider contains a single disulfide bridge Cys4‐Cys10. Oxt 4a assumes a torpedo‐like structure in detergent micelles with an amphipathic α‐helical body (residues 12‐25) and a disulfide‐stabilized head loop (1‐11). Oxt 4a possesses cytolytic and antimicrobial activity and exhibits similarity with Rana‐box peptides from ranid frogs